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Recovery Act Funds Help To Haul in a Gene of Interest

March 9, 2010

Photo of Andrea Moreira and Dr. Tracie Ferreira

Andrea Moreira (seated) pictured with Dr. Tracie Ferreira.

In 1841, the 21-year-old novelist-to-be Herman Melville boarded a whaling ship in New Bedford, Massachusetts and embarked upon a five-year journey that profoundly changed his outlook on life. As Melville later declared in the novel Moby Dick, "A whale ship was my Yale College and my Harvard."

Almost 170 years later, New Bedford still embraces its proud heritage as "The Whaling City." But for Dr. Tracie Ferreira and her students from the New Bedford-Fall River area, about 50 miles south of Boston, their Harvard and Yale is the nearby University of Massachusetts at Dartmouth, and their new outlook on life comes not from a whale but from probing the DNA of the freshwater zebrafish.

Last November, with funds from the American Recovery and Reinvestment Act, the NIDCR issued a $201,318, multi-year grant to the Ferreira laboratory to map the location of a gene that, when experimentally mutated, causes embryonic zebrafish to develop without ever forming the needed cartilage in their faces. The implication being, this gene could be a key component in craniofacial development in vertebrates, or animals with backbones, including humans.

As intriguing as the scientific possibilities are, Ferreira said the grant means so much more to her laboratory. "I tell the students here that I don't do the science to become famous one day but to help them better their lives," said Ferreira, an assistant professor in the Department of Biology. "Most are children of immigrants, primarily from Portugal, and this grant allows them to get hands-on experience, learn new laboratory techniques, and ultimately embark on productive careers in science. It's a win-win situation for everyone."


Zebrafish, or Danio rerio, are striped, carp-like fish native to Asia. Since the early 1980s, scientists have exploited the short generation times, rapid development, and other experimental advantages of zebrafish to study the genetics of vertebrate development. Just as umpires count runs, scientists who study zebrafish count what they call a "phenotype." That's a common term in genetics to describe an observable trait or physical change that results after researchers experimentally mutate a gene in the developing fish embryo. Because zebrafish and humans share a common ancestor about 400 million years down the evolutionary ladder, the hope is the phenotypes that emerge can point researchers to individual genes that are fundamental to human development, much like Old English can tell us a great deal about the origins of Modern English.

Seven years ago as a post-doctoral fellow at the Forsyth Institute in Boston, Ferreira and colleagues created random mutations throughout the zebrafish genome, or complete set of genes. The result: The developing embryos lacked cartilage in their faces and had a ghost-like appearance. Ferreira said tracking down the specific gene responsible for the ghost phenotype might provide valuable clues into the genetics of facial development. The problem was the popular technique that Ferreira employed produces mutations randomly, leaving behind few clues of its location within the estimated 2 billion individual units, or bases, of zebrafish DNA.

Ferreira, who had NIH support at Forsyth to study a common growth factor called TGF-beta in craniofacial development, received thereafter from NIH a four-year, K22 grant, a combination training-and-research grant that helped her make the transition to an independent researcher. She brought the grant with her to UMass-Dartmouth, which enabled her to establish one of a handful of biomedical research laboratories at the university. As Ferreira explained, the laboratory served two purposes – advance craniofacial research and "open the eyes of my students to what science is all about."

Ferreira explained, "Experiments that are performed in the classroom generally reinforce a theory. They aren't intended to discover something new. The NIH grants allow students to problem solve. Why did or didn't an experiment work out as expected? It's something that we can't teach to 20 kids at a time."

After three years and a great deal of problem-solving later, the needle-in-a-haystack search for the gene had narrowed considerably. But the Ferreira lab still had a ways to go until they finished the job. And that's where the Recovery Act funds became critical.

Ferreira said the grant, her first new NIH funding since arriving at the college, allowed her to keep the laboratory running at full throttle and have the means to support two students who are leading the gene hunt. She estimates that over the course of the three-year grant, approximately six to eight students will directly benefit from the Recovery Act funds.

Among them is Andrea Moreira, 24, a graduate student in the university's biology program and the current leader of the gene-mapping project. Although raised and educated in Dartmouth, her parents immigrated to the United States from Portugal in the 1980s. "When I was growing up, my parents worked in the factories," said Moreira. "But over the years, the factories have closed down. So a lot of people now commute long distances to work construction or other jobs on Cape Cod and elsewhere."

Last summer, Moreira joined the caravan of taillights – but for a different reason. She spent the summer at Boston's Children's Hospital learning various laboratory techniques to help her and other UMass-Dartmouth colleagues find the gene. "Going to Boston introduced me to a whole realm of techniques and concepts," said Moreira, who worked in the Chen laboratory. "I think I'm the only one here in the biology department who is doing the gene mapping, and I can teach others in the department how to do it."

Ferreira said that's exactly the point. "Our science graduates compete with kids who graduate from Harvard, Yale, and the other big schools to get research jobs," she continued. "So, they really need the hands on skills to compete. They need that letter from a principal investigator saying, 'She worked in my lab and her experiments came out beautifully.'"

According to Moreira, things are indeed going beautifully in the lab right now. "We've pinned down the gene's location to two flanking markers," said Moreira, who plans to work in the biotechnology industry following graduation. "So, we're making progress, but you never realize how much work goes into something until you're actually doing it."

Background on NIH and Recovery Act

The Recovery Act was signed into law February 17, 2009 to help stem the current economic crisis. It aims to create and save millions of jobs, advance American innovation, and lay a stronger economic foundation to grow the economy in the 21st century.

The Recovery Act made $10.4 billion available to NIH through September 2010 to expand public support for the most promising research ideas, construct and improve laboratory facilities, and purchase needed scientific equipment to enable the work.

Of the $10.4 billion, NIH has transferred $7.4 billion directly to its 27 institutes and centers and the NIH Common Fund, which supports cross-cutting research programs that involve multiple institutes. Based on its percentage of the total annual NIH budget appropriation, NIDCR received a two-year allocation of $101.8 million.

This article originally appeared on the National Institute of Dental and Craniofacial Research website.

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